Viral diseases of the central nervous system (CNS) usually occur as a complication rather than a normal consequence of infection. Nevertheless, many members of the myxo-, paramyxo-, arena-, bunya- and rhabdovirus families, either exceptionally or as a normal consequence, infect the CNS, causing encephalitis or meningitis. Despite their importance to medical neurology, very little is known about the regulation and mode of replication of these viruses in the host organism. Furthermore, virus infections also are distinguished in that they frequently elaborate defective interfering (DI) particles and exhibit evidence of autointerference and viral persistency. The long range objective of this project is the description of the component molecular events involved in the replication of the negative strand viruses. The topics that are currently being investigated are: 1. The origin of DI particles. 2. The primary structure of the gene coding for the VSV L protein (the RNA polymerase). Toward these ends, we have cloned the L gene using recombinant DNA techniques and have determined the nucleotide sequence of this massive gene (6,400 bases). Analysis of this sequence revealed the primary amino acid sequence of the protein and had identified several regions of the chromosome that are important to DI particle formation.